Ruxolitinib is a selective JAK1/JAK2 tyrosine kinase inhibitor developed cooperatively by Incyte Corporation and Novartis Corporation. It is the first drug (Trade name: Jakafi) approved by the US FDA in November 2011 for the treatment of myelofibrosis, and indications thereof are intermediate or high-risk myelofibrosis, including primary myelofibrosis, secondary polycythemia myelofibrosis and post-essential thrombocythemia myelofibrosis. New indications approved by FDA in December 2014 are polycythemia vera with an inadequate response to or intolerance of semicarbazide. In August 2012, it was approved for marketing by the European Union (Trade name: Jakavi); and in July 2014, it was approved for marketing in Japan.
The chemical name of ruxolitinib is (R)-3-cyclopentyl-3-(4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl)propanenitrile, and its structural formula is shown in Formula I:

WO2007070514, WO2010039939, WO2010116282, US20090181959 and Org Lett, 2009, 10(9): 1999-2002 respectively disclose the methods for preparing ruxolitinib and related intermediates, and Drugs of the Future (2010), 35(6), 457-465 provides a review of the above disclosed methods. In the route disclosed in the review, the chiral resolution is set close to the step of forming a final product, and the atomic utilization rate is relatively low and the cost is relatively high. Moreover, the structure of the chiral catalyst is relatively complex and the amount of the catalyst used therein is relatively high. The ee value of the product obtained by chiral resolution is not high, the chiral purity can only reach about 90%, and the product still needs to be resolved or subject to a multi-step refining process to obtain a product with medicinal value.
Angew. Chem. Int. Ed. 2015, 54, 7149-7153 discloses another method for preparing ruxolitinib, in which the amounts of rhodium catalyst and its metal ligand used therein are relatively high and the reaction conditions are harsh. This method is not conducive to large-scale production in view of cost and operation.
In order to overcome the shortcomings of the synthesis processes as described above, the present application aims to provide a new method for preparing ruxolitinib, which is suitable for industrial production.